Dwight Trisha, Thoppe Srinivasan R, Foukakis Theodoros, Lui Weng O, Wallin Göran, Höög Anders, Frisk Tony, Larsson Catharina, Zedenius Jan
Endocrine Tumor Unit, Department of Molecular Medicine, Karolinska Hospital CMM L8:01, Stockholm, SE-171 76 Sweden.
J Clin Endocrinol Metab. 2003 Sep;88(9):4440-5. doi: 10.1210/jc.2002-021690.
Recently, a translocation t(2; 3)(q13;p25), involving the fusion of PAX8 and peroxisome proliferator-activated receptor gamma (PPAR gamma) was suggested to arise only in follicular thyroid carcinomas. In this study, a group of 87 thyroid tumors were analyzed to determine the involvement of the PAX8/PPAR gamma fusion gene in these tumors, and also to determine whether this rearrangement can be used as a diagnostic marker for the differentiation between follicular thyroid carcinoma and adenoma. The PAX8/PPAR gamma rearrangement was detected by RT-PCR, fluorescence in situ hybridization, and/or Western analysis in 10 of 34 (29%) follicular thyroid carcinomas and in one of 20 (5%) atypical follicular thyroid adenomas, but not in any of the 20 follicular thyroid adenomas or 13 anaplastic thyroid carcinomas studied. In addition, seven of the 87 thyroid tumors exhibited involvement of PPAR gamma alone. Our findings suggest that PAX8/PPAR gamma occurs frequently in follicular thyroid carcinomas, and the presence of this rearrangement is likely to prove highly suggestive of a malignant tumor. Lack of the PAX8/PPAR gamma rearrangement in the anaplastic thyroid carcinoma group suggests that the tumorigenic pathway in these tumors is likely to be independent of this fusion. Furthermore, the results suggest that other rearrangements, involving PPAR gamma and other unidentified genes, may be involved in follicular thyroid tumorigenesis.
最近，一种涉及PAX8与过氧化物酶体增殖物激活受体γ（PPARγ）融合的t(2; 3)(q13;p25)易位被认为仅出现在滤泡状甲状腺癌中。在本研究中，对一组87例甲状腺肿瘤进行了分析，以确定PAX8/PPARγ融合基因在这些肿瘤中的情况，同时确定这种重排是否可作为滤泡状甲状腺癌与腺瘤鉴别的诊断标志物。通过逆转录聚合酶链反应（RT-PCR）、荧光原位杂交和/或蛋白质免疫印迹分析，在34例滤泡状甲状腺癌中的10例（29%）以及20例非典型滤泡状甲状腺腺瘤中的1例（5%）检测到了PAX8/PPARγ重排，但在所研究的20例滤泡状甲状腺腺瘤或13例未分化甲状腺癌中均未检测到。此外，87例甲状腺肿瘤中有7例仅表现为PPARγ受累。我们的研究结果表明，PAX8/PPARγ在滤泡状甲状腺癌中频繁出现，这种重排的存在很可能强烈提示为恶性肿瘤。未分化甲状腺癌组中缺乏PAX8/PPARγ重排表明，这些肿瘤的致瘤途径可能独立于这种融合。此外，结果表明，涉及PPARγ和其他未鉴定基因的其他重排可能参与了滤泡状甲状腺肿瘤的发生。
